The Neuropathology Core for this Program Project Grant is a laboratory function dervied from neurohistochemistry and imunostaining capabilities that currently exist in the research laboratories of Drs. Davidson and Moore. Formalization of this laboratory function as the Neuropathology Core housed within Dr. Moore's research laboratory will centralize personnel, equipment, and reagents necessary to efficiently produce high quality brain sections and stains ready for microscopic evaluaton. The Neuropathology Core facility's overall objective is to support Drs. Davidson, Paulson, Kosik, Gonzalez-Alegre, and Dauer in the evaluation of mouse brains following transduction with viruses expressing specific shRNAs. This includes consultation with Program investigators concerning the processing of brains for microscopic evaluation, development of specific immunostaining or histochemical staining protocols, production of high quality brain sections, and staining sections for evaluation in individual investigator laboratories. The Neuropathology Core staff and investigators are in close contact through all phases of this process. Thus, the Core serves as both a research and development facility for histology-based methods and a service facility to provide brain sections ready for microscopic evaluation. In addition, Dr. Moore (a board-certified neuropathologist) will provide standard neuropathologic evaluation of brain sections as needed for each project. This latter responsibility is particularly important in the objective evaluation of transduced brains for untoward effects of RNAi. The main responsibilities of the Core will be: 1) Complete the processing of brains for histologic evaluation; 2) Produce microscopic sections specifically adapted to the needs of each project; 3) Produce histochemical or immunostained slides as needed by each project; 4) Store uncut tissue and unstained sections; 5) Evaluate brains for general neuropathological changes as needed by each project; 6) Develop new staining methods for use in individual projects.